Infertility affects 10 to 15 percent of the U.S. population, with
about half of those cases involving problems with male fertility.
One of the mysteries of infertility is that
sperm quality and quantity seem to have little to do with
whether or not a man is fertile.

"In 70 percent of men, you can't predict their fertility on the
basis of sperm count and routine assessment of quality," said
researcher Gary Cherr at the University of California at Davis.

The new clues regarding infertility that Cherr and his colleagues
discovered have to do with a gene called DEFB124 that encodes
beta-defensin 126, which belongs to a germ-killing class of
proteins. A thick coat of this molecule is applied onto sperm in
the coils of the epididymis, the structure where sperm are stored
after they are generated in the testicles. [ 5 Myths
About the Male Body ]

Beta-defensin 126 helps sperm swim through the mucus in the
cervix, the neck of the womb. As such, it acts kind of like a
"Klingon cloaking device," Cherr said, helping sperm sneak their
way to an egg.

Men with two mutant copies of DEFB124 lack beta-defensin 126.
Their sperm look and swim normally when seen under a microscope;
however, the scientists discovered the little swimmers are about
85 percent less able to make their way through an artificial gel
resembling human cervical mucus, revealing how this genetic
defect likely accounts for many hitherto unexplained cases of
infertility.

In an analysis of more than 500 newly married Chinese couples,
the investigators found men who had two mutant copies of the gene
had lowered fertility — their wives were 40 percent less likely
to become pregnant than other couples. This even proved true of
men with the mutation who did not display other problems
typically linked with infertility, such as low sperm count and
reduced sperm motility.

The mutation is not limited to China. A survey of DNA samples
from the United States, United Kingdom, China, Japan and Africa
showed that about half of all men carry one defective copy of
DEFB126 and about a quarter have two mutant copies.

The upshot

These findings are surprising, as one might expect a mutation
that dramatically affects fertility to be much less common, since
carriers would have less offspring and thus make up less of the
population. It may be that men with one normal and one defective
gene but
normal fertility are advantaged in some way, speculated
researcher Ted Tollner at the University of California at Davis.

Another possibility is that because humans breed in long-term
monogamous relationships, unlike most mammals, sperm quality does
not matter as much, Cherr suggested. Tollner noted that human
sperm are typically slow swimmers with a high rate of defects
when compared with that from monkeys and other mammals.

However, some researchers do think that human fertility has been
falling worldwide in recent decades. That problem could be linked
with the commonality of defects in this gene. Cherr said the
researchers next hope to work with a major U.S. infertility
program to explore the role of the mutation. [ 5
Myths of Fertility Treatments ]

Future research could lead to bothclinical and home infertility
tests looking for this mutation. Couples then could be treated
with a procedure known as intracytoplasmic sperm injection or
ICSI, in which eggs are removed from a woman and injected
directly with sperm, avoiding an expensive workup to exclude
other causes, said male infertility specialist John Gould at the
University of California at Davis.

Another possible intervention for such couples might ultimately
be synthetic forms of beta defensin 126 that can be added to
sperm. "You can concentrate it in a vaginally applied cream or
gel, and sperm would pick up this defensin coat as they advanced
into the cervix," Cherr said.

Ironically, although these findings hold the promise of
fertility, they owe their origins to research into a novel type
of contraceptive. The scientists were investigating proteins
coating sperm for potential targets of a vaccine — the immune
systems of recipients of such a treatment would then go on to
recognize and destroy sperm, Tollner told LiveScience.

"We didn't investigate this for purposes in humans, but for
purposes in canines — to help manage dog and cat populations,"
Tollner explained. There is research into such
immunocontraceptive vaccines for humans, but he noted the
resulting contraceptive effect appears only temporary.

The scientists detailed their findings online July 20 in the
journal Science Translational Medicine.